United States: New Reprint Guidance Maintains Bipartisan Status Quo

Last Updated: March 13 2014
Article by Kenneth J. Wilbur

On February 28, 2014, the FDA issued its most recent unofficial guidance on distribution by manufacturers of research concerning off-label uses.1  With minor textual revisions, this new Guidance essentially restates the safe harbors acknowledged in FDA's unofficial 2009 "Good Reprint Practices" Guidance2, and expands them to medical reference texts and clinical practice guidelines.  Under the 2014 Guidance, drug and device manufacturers can engage in some forms of distribution of peer-reviewed research about off-label use of their products without fear this will be used as evidence of misbranding.  In not backtracking from the 2009 reprint reforms, but rather expanding them to embrace other forms of communication, the 2014 Guidance represents continued evolution of FDA's position on speech concerning off-label use.

This evolution has been tortuous.  FDA's initial position, in the early 1990s, was that manufacturers were prohibited from providing doctors with any unsolicited information about use of their products for uses not approved (i.e. "indicated") on product labels.  Originally, FDA attempted to enforce its position, while evading judicial review of its constitutionality, through issuing informal warning letters threatening misbranding actions whenever a manufacturer engaged in communications discussing off-label uses.  After a judicial decision refused to condone FDA engaging in censorship through ad terrorem threats of prosecution3, in 1996 FDA issued a Guidance which finally made an overt assertion that manufacturers could not distribute reprints or enduring materials like textbooks discussing off-label uses, but were limited to distributing reprints discussing only on-label uses.4  Congress itself found FDA's policy too restrictive, and in 1997 permitted manufacturers to distribute reprints discussing non-approved uses, at least when an application for approval of that use was pending.5  The District Court for the District of Columbia found both the 1996 Guidance and the relevant provisions of the Food and Drug Administration Modernization Act (FDAMA) unconstitutional, and put in place an injunction permitting manufacturers to distribute materials from bona fide peer-reviewed journals and textbooks.6  On appeal, FDA, which had already abandoned defense of the 1996 Guidance, mooted the case by conceding that neither the FDAMA nor a 1997 Guidance on continuing medical education gave it any enforcement authority, but merely identified safe harbors within which FDA agreed that it would not seek to restrict manufacturer dissemination of information discussing non-approved uses of their products.7

In some ways resembling the armistice ending the Korean Conflict, the 2000 Court of Appeals decision in WLF v. Henney left the FDA and manufacturers engaged in an armed truce on opposite sides of the First Amendment.  FDA had tacitly acknowledged the First Amendment protects some forms of distribution of materials discussing off-label uses beyond the conservative minimum safe harbor recognized in the FDAMA, and manufacturers had recognized there is an undefined line – perhaps not quite as liberal as the WLF injunction — which, if crossed would  subject them to the sledgehammer of a misbranding prosecution.  Following the FDAMA expiring by its own terms in 2006, FDA, in an effort at agency-industry détente, sought to define this de facto status quo in its 2009 Good Reprint Practices Guidance.  In the 2009 Guidance, FDA for the first time acknowledged that manufacturers could distribute to doctors, without a prior request from the doctor for information,8 some unabridged, unedited and un-highlighted reprints of articles primarily written by independent researchers published in bona fide peer-reviewed journals.  This position is carried forward – in many cases in near-identical language – in the new 2014 Guidance.

In the 2014 Guidance, like its 2009 predecessor, FDA seeks to preserve awareness of the distinction between on- and off-label uses by imposing some "time, place and manner" restrictions separating dissemination of off-label materials from distribution of promotional materials concerning approved uses.  The Guidance requires disclaimers that the distributed reprint concerns a use which had not been approved by FDA, discussing all significant risks or safety concerns known to the manufacturer concerning the unapproved use, and enclosing the FDA-approved label.  The Guidance also requires a conflict of interest disclosure of the manufacturer's interest in the drug and any ties of any author to the manufacturer.  The Guidance also calls for the reprinted article to be distributed with a comprehensive bibliography of adequate and well-controlled studies about the use of the product and, where one exists, a representative publication coming to a different conclusion about the off-label use.

Where the 2014 Guidance goes beyond the 2009 Guidance is in extending the substance of the reprint safe harbors to medical reference texts, which had been covered by the 1996 Guidance but as to which  the 2009 Guidance was silent.  In applying the reprint safe harbors to textbooks, the 2014 Guidance makes some adjustments necessitated by the different context of medical texts.   For example, whereas redistribution of the entire unedited work is required for journal reprints, redistribution of relevant chapters of a medical reference text is permitted.  The 2014 Guidance also applies, with  similar contextual adjustments,  to Clinical Practice Guidelines (CPG) intended to help clinicians make decisions for individual patient care in situations where there are few or no approved products.  Here, the primary restriction relates to a requirement that the CPG be "trustworthy" in that it conform to Institute of Medicine's standards to ensure that the CPG reflects an adequate systemic review of evidence and assessment of the benefits and harms of alternative care options.

It would be an exaggeration to say the 2014 Guidance reflects a full embrace by FDA of the First Amendment.  It fails to acknowledge the changed landscape resulting from recent pro-speech Supreme Court decisions9 and in some instances clings to regulatory theories called into question by United States v. Caronia,10 a decision it studiously ignores.  There has also been long-standing criticism of the First Amendment validity of some of the restrictions in the 2009 Guidance.  In particular, a narrow interpretation of the requirement that reprints discuss only what FDA considers "adequate and well-controlled clinical investigations" – a threshold not always attainable for some off-label uses that may nevertheless represent the standard of care – could become a pretext for censorship and represent a significant government intrusion into clinical research.  The same is true with respect to the requirement that the reprinted article not be "significantly" influenced by anyone having ties to the manufacturer, as it is  common for some of the researchers involved in studies examining cutting edge uses to have ties to the manufacturers who are most interested in exploring these issues. The WLF injunction had, pointedly, sought to address this issue by requiring disclosure of these interests,  not a bar on circulating publications in which researchers with ties to the manufacturer were involved.  Finally, in practice, the required steps to segregate distribution of reprints from promotional materials at conferences can become an issue of form over substance, while FDA's efforts to regulate exactly what a manufacturer's representative can say when handing the reprint to a doctor give rise to obvious substantive and practical problems in reconciling enforcement with the First Amendment, particularly in light of the Second Circuit striking down the enforcement efforts in Caronia.

These details, however, are issues to resolve another day.  Perhaps the most important take-away from the 2014 Guidance is that in it, the Obama Administration did not back away from, but instead essentially embraced and even mildly expanded, an approach outlined in the waning days of the Bush Administration.  The 2009 and 2014 Guidances together thus reflect a bipartisan consensus that manufacturers should be able to distribute some peer-reviewed research about off-label uses:  a striking, and welcome, departure from the Agency's initial pro-censorship position in the 1990s.


1 Guidance for Industry – Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices.  FDA February 2014.  Available here.

2 Guidance for Industry – Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.  FDA, January 2009.  Available here.

3 Washington Legal Foundation v. Kessler, 880 F. Supp. 26, 36 (D. D.C. 1995).

4 Guidance to Industry on Dissemination of Reprints of Certain Published, Original Data and Guidance for Industry Funded Dissemination of Reference Texts.  61 Fed. Reg. No. 196 (Oct. 8, 1996).  Available here.

5 See Food and Drug Administration Modernization Act (FDAMA), 21 U.S.C. § 360aaa.

6 Washington Legal Foundation v. Henney, 56 F. Supp. 2d 81, 88 (D.C. Cir. 1999).

7 Washington Legal Foundation v. Henney, 202 F.3d 331 (D.C. Cir. 2000).

8 A separate series of informal Guidances have addressed what manufacturers can provide in response to a request for information.  Responding to Unsolicited Requests for Off-Label Information about Prescription Drugs and Medical Devices, December 2011 (available here).

9 See, e.g., Sorrell v. IMS Health, Inc., 131 S.Ct. 2653, 2670-71 (2011).

10 703 F.3d 149 (2d Cir. 2012),  Most tellingly, while repeating a long regulatory history discussion originally advanced to defend the now-defunct 1996 Guidance, the 2014 Guidance's "Background" discussion does not address the Second Circuit's finding in Caronia that FDA could not punish manufacturers merely for disseminating truthful, non-misleading materials about off-label use of their products.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Kenneth J. Wilbur
In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:
  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.
  • Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.
    If you do not want us to provide your name and email address you may opt out by clicking here
    If you do not wish to receive any future announcements of products and services offered by Mondaq you may opt out by clicking here

    Terms & Conditions and Privacy Statement

    Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

    Use of www.mondaq.com

    You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


    Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

    The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


    Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

    • To allow you to personalize the Mondaq websites you are visiting.
    • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
    • To produce demographic feedback for our information providers who provide information free for your use.

    Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

    Information Collection and Use

    We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

    We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

    Mondaq News Alerts

    In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


    A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

    Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

    Log Files

    We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


    This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

    Surveys & Contests

    From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


    If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


    From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

    *** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


    This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

    Correcting/Updating Personal Information

    If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

    Notification of Changes

    If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

    How to contact Mondaq

    You can contact us with comments or queries at enquiries@mondaq.com.

    If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.

    By clicking Register you state you have read and agree to our Terms and Conditions